Predicting recurrence of non-muscle-invasive bladder cancer following instillati
PUBLISHED: 2015-11-30  385 total views, 1 today

Yu Xie1, Gang Fan2, Chun Liu2, Jian Lei2, Mingji Ye2Zhengzhou Xu2, Weiqing Han2 

1Urology Department,Hunan Provincial Cancer Hospital, The affiliated Cancer Hospital of XiangyaMedical College, Central South University, 2The affiliated CancerHospital of Xiangya Medical College, Hunan Provincial Cancer Hospital

 


Objective:The standard treatment for patients withnon-muscle-invasive bladder cancer (NMIBC) is intravesical therapy followingtransurethral resection of bladder tumor (TURBT). However, only approximately10% to 40% of the patients can obtain disease-free survival for five years. Forhigh-risk patients, the disease progression rate for five years is raised to47%. Therefore, this study searches for an effective molecular predictivemarker for the identification of the instillation of chemotherapy sensitivityof patients with NMIBC. Transcription factor TFAP2α is a member of the AP-2family that can function as a tumor suppressor by regulating various genesinvolved in cell proliferation and apoptosis. Chemotherapeutic drugs, such ascisplatin, induce post-transcriptionally endogenous AP-2a, which contributes tochemosensitivity by enhancing therapy-induced apoptosis. Method: In thisstudy, the transcription factor AP-2a was selected from a previously identifiedfactor for predicting recurrence in NMIBC following the instillation ofchemotherapy. Immunohistochemistry assessed the AP-2a expression in 128 bladdertissues from patients with non-muscle-invasive bladder tumor. All patients werewithout any treatment before TURBT, although they underwent intravesicaltherapy after TURBT. To provide direct evidence for the role of AP-2a in NMIBC,the siRNA knockdown approach was used to suppress its expression in T24, Biu87.Result: Our study results showed that AP-2a was a strong independentpredictive marker for NMIBC patients treated with intravesical therapyfollowing TURBT. The patients with strong AP-2a staining had satisfactorydisease-free survival, whereas the patients with weak AP-2a staining hadhigh-risk of recurrence. Patients with the same levels of AP-2a protein couldobtain similar disease-free survival although they received different perfusiondrugs. In vitro studies demonstrate that bladder cell lines T24 and Biu87decreased sensitivity to pirarubicin and hydroxycamptothecin throughtransfection with siRNA targeting AP-2a transcript. Conclusion: Laboratorywork presented evidence that AP-2a may be involved in the regulation ofsensitivity of intravesical therapy in patients with pirarubicin andhydroxycamptothecin. AP-2a may have predicting recurrence potential for NMIBCpatients with chemotherapy.

 



Key Words: AP2a, Chemosensitivity,Bladder cancer


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